Prognostic Significance of Chromosome Aberrations in High-Grade Soft Tissue Sarcomas (original) (raw)
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Cancer research, 2002
Cytogenetic analysis has not only provided important information on the pathogenesis of soft tissue tumors but, by disclosing distinct chromosomal rearrangements in different histopathological entities, has also come to serve as a valuable diagnostic tool. Little is known as yet about the potential prognostic impact of cytogenetic features detected in these tumors. A total of 239 benign and 221 malignant soft tissue tumors with clonal chromosome aberrations were subdivided according to general karyotypic features, such as degree of complexity and ploidy level, and rearrangements of specific chromosomal regions. The cytogenetic variables were analyzed regarding clinical outcome, using time to metastasis as the end point. Selected variables were then compared with established clinicopathological predictors of metastasis development. When the entire material was considered, 167 of 268 investigated cytogenetic variables were associated with clinical outcome. Focusing on the subset of 15...
International Journal of Cancer, 1997
The most important prognostic factor in soft tissue sarcomas (STS) is tumor grade. Since most grading methods are subject to the interpretation of the individual pathologist, there is a need for objective criteria such as DNA ploidy and karyotype, which are of prognostic value in several types of malignancy. We have analyzed the relationships among tumor grade, DNA ploidy, cytogenetic abnormalities and the clinical outcome of 44 previously untreated patients with 12 different histological types of primary STS. The tumors were graded according to the method of Coindre, which resulted in 9 grade I (20%), 18 grade II (41%) and 17 grade III (39%) STS. DNA flow cytometry and chromosomal analysis were performed using standard techniques. After a median follow-up time of 39 (range, 2-124) months, Kaplan-Meier survival analysis was performed. Significant differences in 5-year overall survival were found between patients with grade I or II and grade III STS (p F 0.05). Seventeen STS were aneuploid and 26 were euploid. In 21 of 39 successfully cultured STS an abnormal karyotype was found. There were no significant differences in survival in relation to DNA ploidy or the presence of chromosomal abnormalities. Our results show that grading had higher prognostic value than DNA ploidy or the presence of cytogenetic abnormalities in this heterogeneous group of STS. Int.
The role of cytogenetics and molecular diagnostics in the diagnosis of soft-tissue tumors
Modern Pathology, 2014
Soft-tissue sarcomas are rare, comprising o1% of all cancer diagnoses. Yet the diversity of histological subtypes is impressive with 4100 benign and malignant soft-tissue tumor entities defined. Not infrequently, these neoplasms exhibit overlapping clinicopathologic features posing significant challenges in rendering a definitive diagnosis and optimal therapy. Advances in cytogenetic and molecular science have led to the discovery of genetic events in softtissue tumors that have not only enriched our understanding of the underlying biology of these neoplasms but have also proven to be powerful diagnostic adjuncts and/or indicators of molecular targeted therapy. In particular, many soft-tissue tumors are characterized by recurrent chromosomal rearrangements that produce specific gene fusions. For pathologists, identification of these fusions as well as other characteristic mutational alterations aids in precise subclassification. This review will address known recurrent or tumor-specific genetic events in soft-tissue tumors and discuss the molecular approaches commonly used in clinical practice to identify them. Emphasis is placed on the role of molecular pathology in the management of soft-tissue tumors. Familiarity with these genetic events provides important ancillary testing for pathologists to include in their diagnostic armamentarium.
Curent concepts in pathology of soft tissue sarcoma
Indian journal of surgical oncology, 2011
Soft tissue sarcomas (STS) constitute a heterogeneous category of soft tissue neoplasia composed mostly of uncommon tumors of diverse histology, different biology and varied outcomes. Substantial developments in immunohistochemistry (IHC), cytogenetics and molecular genetics of STS have caused a significant change in the classification and diagnosis of these tumors with a direct implication for clinical management and prognosis. In this review we discuss newer developments impacting diagnosis and prediction.
Increased risk of malignancies in a population-based study of 818 soft-tissue sarcoma patients
British journal of cancer, 2006
Soft-tissue sarcomas (STS) have been associated with various rare cancer syndromes and occur at increased frequencies in survivors of childhood cancer. Also adult patients with STS have been suggested to be at an increased risk of additional malignancies. After exclusion of syndrome-associated and radiation-induced sarcomas, we studied multiple primary malignancies in a population-based cohort of 818 patients with primary STS of the extremities and the trunk wall. In total, 203 other malignancies developed in 164 (20%) patients median 10 (0-32) years before and median 4 (0-35) years after the sarcoma diagnosis. Standardised morbidity ratios (SMRs) were determined for primary malignancies following a STS. Hereby individuals who had developed a STS were identified to be at increased risk of second primary malignancies (SMR for all malignant tumours=1.3; 95% CI=1.0-1.5; P=0.02) with STS being the only specific tumour type that occurred at an increased risk (SMR=17.6; 95% CI=8.1-33.5; P...
Identification of low-risk tumours in histological high-grade soft tissue sarcomas
European Journal of Cancer, 2007
Growth pattern Size Necrosis A B S T R A C T In more than one-third of patients with a histological high-grade malignant soft tissue sarcoma metastasis develops despite local control of the primary tumour. Hence, adjuvant chemotherapy is increasingly used for these relatively chemoresistant tumours which requires improved prognostication to exclude low-risk patients from overtreatment. We assessed the value of stepwise prognostication in a series of 434 histological high-grade STS of the extremity and trunk wall. Vascular invasion was used as the first discriminator whereafter the risk factors tumour necrosis, size (>8 cm) and infiltrating growth pattern were used to discriminate high-and low-risk tumours. We identified a high-risk group with a cumulative incidence of metastasis >0.4 at 5 years, and a low-risk group, comprising half of the tumours, with a cumulative incidence of metastasis <0.15. The model was validated in an independent material of 175 patients. This model improved prognostication in STS and is of value for identifying patients who probably should not receive adjuvant chemotherapy.
A retrospective statistical analysis of high-grade soft tissue sarcomas
Medical Oncology, 2011
Soft-tissue sarcomas have a mortality rate ranging from 40-60% for high-grade lesions. Prior identified risk factors for post-surgical mortality include tumor size, lesion histology, and margin status at resection. A better understanding of prognostic factors is needed to guide patient counseling and treatment. Data were collected from 129 patients surgically treated for high-grade extremity soft tissue sarcomas during 2002-2010. The primary endpoint was death related to high-grade soft tissue sarcoma. Thirteen variables were investigated: age, gender, race, tumor size, margin status, location, estimated blood loss, operative blood transfusions, pre-operative metastatic disease, pre-operative radiation, post-operative radiation, pre-operative chemotherapy, and post-operative chemotherapy. A Cox Survival Analysis model was created to determine the best predictors of survival time. Tumor size and the presence of pre-surgical metastasis were statistically significant predictors of overall survival. Patients with a tumor greater than 8 cm in any cross section had a 3.15 times greater chance of death. Presence of pre-surgical metastasis carried a 3.47 greater chance of death. The remaining variables did not predict patient outcomes in a statistically significant manner. The hazard ratios calculated add new data and can be used to more effectively guide patients in prognosis and treatment regimens.
Cancer, 1984
A multidisciplinary study of 163 patients treated at the NCI for soft tissue sarcomas allowed the correlation of a number of histologic features (histologic type, mitosis, necrosis, pleomorphism, cellularity, and matrix) of the primary lesion to time to recurrence and overall survival of the patients. The results of the stratified analyses show that necrosis is the single best histopathologic parameter to predict the time to recurrence (P = 0.025) and the overall survival of the patients ( P = 0.002). Necrosis in the primary lesion is also of value in predicting survival after the first recurrence has taken place (P = 0.001). The value of necrosis in the primary lesions predicting the clinical course after recurrence appears to be independent of age, sex, location, and size of the tumor. The authors propose a grading system based on histologic typing and histologic parameters to identify a group of lesions with minimal metastatic potential (Grade l), and on the use of necrosis to distinguish between aggressive lesions with good patient survival (Grade 2) and aggressive lesions with poor patient survival (Grade 3).